Activation of tyrosine kinases is an important factor during cancer development. Axl, one of the receptor tyrosine kinases, binds to the specific ligand growth arrest-specific gene 6 (Gas6), which encodes a vitamin K-dependent gamma-carboxyglutamyl protein. Although many receptor tyrosine kinases and their ligands are involved in gastric carcinogenesis, whether Gas6-Axl signaling is involved in gastric carcinogenesis has not been elucidated. The aim of this study was to investigate the expression of Gas6 and Axl in gastric cancer and also their roles during gastric carcinogenesis. mRNA and protein of Gas6 and Axl were highly expressed in a substantial proportion of human gastric cancer tissue and cell lines, and Gas6 expression was significantly associated with lymph node metastasis. With recombinant Gas6 and a decoy-receptor of Axl in vitro, we demonstrated that Gas6-Axl signaling pathway enhanced cellular survival and invasion and suppressed apoptosis via Akt pathway. Our results suggests that Gas6-Axl signaling plays a role during gastric carcinogenesis, and that targeting Gas6-Axl signaling could be a novel therapeutic for gastric cancer.

SG compression therapy is effective for reducing nab-PTX-induced peripheral neuropathy. The nab-PTX exposure to the peripheral nerve may be decreased because the SG decreases microvascular flow to the fingertip.

The 21-gene reverse transcriptase-polymerase chain reaction assay with a patented algorithm is validated as a good predictor of prognosis and potential benefit from adjuvant chemotherapy for lymph-node-negative, estrogen-receptor-positive, early-stage breast cancer, while its high cost raises concern about how to finance it. Cost-effectiveness analysis comparing prevalent National Comprehensive Cancer Network (NCCN) guideline/St Gallen recommendation-guided treatment with the assay-guided treatment is carried out with budget impact estimation in the context of Japan's health care system. Incremental cost-effectiveness ratios are estimated as 2,997,495 yen/QALY (26,065 US$/QALY) in the comparison between NCCN guided-treatment vs. the assay-guided treatment, and as 1,239,055 yen/QALY (10,774 US$/QALY) in the comparison between St Gallen guided-treatment vs. the assay-guided treatment. Budget impact is estimated as yen2,638 million (US$23 million) to yen3,225 million (US$28 million) per year. The routine use of the assay is indicated as cost-effective. And the budget impact could be judged as within fundable level.

This retrospective study clarifies the prevalence and risk factors for BM and SRE in Japanese breast cancer patients. Our results show the importance of considering subtype in the care of BM and SRE.

Abstract.We have previously shown that expression of SIAH1 is frequently down-regulated in HCCs and associated with their advanced stages. It has been shown that SIAH1 functions in the phosphorylation-independent degradation of ß-catenin and induces apoptosis and growth arrest. To examine if the effects of SIAH1 overexpression depend on the altered ß-catenin signaling pathway, we transferred the SIAH1 gene into three hepatoma cell lines with different genetic backgrounds: HepG2 (mutant ß-catenin), SNU475 (mutant AXIN1), and Huh7 cells (wild type ß-catenin and AXIN1). SIAH1 significantly decreased aberrant ß-catenin signal in HepG2 and SNU475 cells and induced growth arrest and apoptosis. However, SIAH1 also induced apoptosis in Huh7 cells, which retained a normal membranous distribution pattern of ß-catenin. Immunoblotting study demonstrated that SIAH1 also reduces the amount of PEG10 protein, which is known to be frequently overexpressed in HCC and to promote cell proliferation. These data suggest that PEG10 is another target protein of SIAH1 to induce apoptosis in hepatoma cells. Our results should lead to a better understanding of the relationship between deregulation of ß-catenin signals and hepatocarcinogenesis. Further investigations into the mechanisms by which SIAH1 promotes apoptosis and suppresses cell growth should also allow for the discovery of new therapeutic strategies. IntroductionHepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. Epidemiological studies have revealed that major causes of HCC are exposure to carcinogens such as aflatoxin B1, cirrhosis of any etiology, or chronic infection to hepatitis B or C. Molecular approaches have disclosed involvement of several genetic alterations in hepatocellular carcinogenesis, including mutation of TP53, ß-catenin and AXIN1 (1-3). Among these, mutation of ß-catenin or AXIN1 has been shown to result in nuclear accumulation of ß-catenin protein. Accumulated ß-catenin is known to associate with the Tcf/Lef family of transcriptional factors thereby activating target genes, such as c-myc and cyclin D1. Immunohistochemical analysis revealed that ß-catenin is aberrantly accumulated in nearly 50% of HCCs (3,4), suggesting that alteration of the ß-catenin signaling pathway is one of the most common and major mechanisms of the development of HCC.We previously performed a fine deletion mapping of chromosome 16 to search for a novel tumor suppressor gene for HCC and identified SIAH1, which is located at a commonly deleted region 16q12.1 (5). Although we did not find any somatic mutation of SIAH1, its expression was markedly down-regulated, especially in cases harboring loss of heterozygosity (LOH) at the SIAH1 locus. Moreover, decreased expression of SIAH1 was associated with the advanced stage of HCCs, suggesting that inactivation of SIAH1 plays an important role in HCC progression (5). SIAH1 is a human homolog of the Drosophila seven in absentia (sina), required for formation of the R7 photoreceptor cells during eye developmen...